for the full 90 days patients were observed in the study, according to data presented last month at the Association for Research in Vision and Ophthalmology (ARVO) conference. The higher the dose, the more effective the drug was at slowing down the rod visual cycle. The highest dose tested, 10 milligrams a day, was well-tolerated and far lower than the 75 milligram dose Acucela tested in an earlier safety study in healthy volunteers.
While that all sounds nice, those results don’t offer the kind of proof Acucela will need to show that this drug is an important advance for age-related macular degeneration. But the study does provide Acucela the evidence it needs to advance to the next stage, the third and final phase of clinical trials normally required for FDA approval of a new drug.
The critical decisions are being made now, which will determine if Acucela has a successful drug, say, five years from now. Many of the details are still being worked out, but here’s what Kubota says to expect:
The next trial will enroll “a few hundred patients,” and it will randomly assign patients to get a dose of the Acucela drug or a placebo. The study will enroll patients with an advanced form of macular degeneration known as “geographic atrophy,” in which small deposits of metabolic byproducts have killed retinal cells in the eye. The main goal will be show, with precise measurement, that the Acucela drug can slow the rate of expansion in that area of atrophied retinal cells.
Because this is a slow-moving disease, patients will have to be followed for two years, Kubota says, although the trial will be designed to provide researchers an interim look at the data to see if the drug is offering a clear benefit before the full two years are up.
Once the key details are worked out—the number of patients, the clinical sites around the world, the exact protocols on who can enroll and who can’t—Acucela hopes to get the study under way in 2013, Kubota says. He didn’t offer a prediction on when Acucela might be able to seek FDA approval, but given how long it takes to enroll patients in clinical trials, and the time of observation required, it’s hard to imagine the company seeking FDA clearance before 2015.
I quizzed Kubota a bit about the validity of the study goal, since other drugs in the past for age-related macular degeneration were required to show they helped patients read more lines on an eye chart. But Kubota says that trial goal, of improved visual acuity, can be misleading because it can be influenced by whether a patient comes in for examination in the morning or the afternoon, or whether they are tired. The FDA, in collaboration with researchers in the field, has determined that slowing the rate of growth in atrophy of the retinal cells is the best way to consistently measure whether a drug is having an impact on a patient’s eyesight.
“Visual acuity isn’t that reliable of an endpoint,” Kubota says.
The bigger question could end up being, essentially, “How much improvement in geographic atrophy is good enough?” While a 50 percent slowdown in the rate of atrophy expansion would be considered a huge success, opinions vary on how clinically meaningful it might be to patients if a drug slows down the rate of atrophy by 10 or 20 percent, Kubota says. Some ophthalmologists say that any improvement that’s statistically significant will be a worthy advance, because patients have no other options, Kubota says.
Like any field of drug development where there are potentially millions of patients involved, Acucela isn’t alone in its pursuit of new therapies for “dry” age-related macular degeneration. GlaxoSmithKline has an antibody drug designed to hit amyloid proteins, which is also in Phase II clinical trials, Kubota says. Cheshire, CT-based Alexion Pharmaceuticals (NASDAQ: [[ticker:ALXN]]) also has an antibody in mid-stage testing. And a new Boston-based startup called Alkeus Pharmaceuticals, with Vertex Pharmaceuticals (NASDAQ: [[ticker:VRTX]]) founder Josh Boger as executive chairman, is going after dry age-related macular degeneration and a couple of other eye disorders.
Kubota, like any entrepreneur, keeps a close watch on his competitors, and can list off a series of reasons why he thinks his drug will be better. Now Acucela’s task is to get the data to prove it. “A lot of people are interested in what we’re doing,” Kubota says.
